Dynamic changes in eIF4F-mRNA interactions revealed by global analyses of environmental stress responses.
Dynamic changes in eIF4F-mRNA interactions revealed by global analyses of environmental stress responses.
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DOI：
10.1186/s13059-017-1338-4
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发表时间：
2017-10-27
期刊：
影响因子：
12.3
通讯作者：
Pavitt GD
中科院分区：
文献类型：
--
作者：
Costello JL;Kershaw CJ;Castelli LM;Talavera D;Rowe W;Sims PFG;Ashe MP;Grant CM;Hubbard SJ;Pavitt GD
翻译因子eIF4E和eIF4G形成eIF4F，与信使RNA (mRNA) 5 '帽相互作用，促进核糖体募集和翻译起始。eIF4F与单个mrna关联的差异可能导致mrna之间翻译起始频率的差异。由于翻译起始受到环境胁迫的全局重编程，我们有兴趣确定eIF4F与单个mrna的相互作用是否被重编程，以及这可能如何促进全局环境胁迫反应。使用标记因子蛋白捕获和rna测序（RNA-seq）方法，我们评估了mRNA与eIF4E， eIF4G1和eIF4G2的关联如何响应三种定义的应激，每种应激都会导致蛋白质合成的快速衰减：过氧化氢诱导的氧化应激和氨基酸或葡萄糖引起的营养应激。我们发现急性应激导致eIF4F-mRNA相互作用的动态和意想不到的变化，这些变化在每个因子和施加的应激之间共享。应激稳定的eIF4F - mrna相互作用主要与翻译抑制有关，而更主动启动的mrna相对而言会被eIF4F耗尽。同时，其他mrna不受这些应激诱导的eIF4F关联变化的影响。动态的eIF4F-mRNA相互作用变化是环境胁迫中共享的协调的早期翻译控制反应的一部分。我们的数据与一个模型兼容，其中多个mRNA闭环复合物形成不同的稳定性。因此，出乎意料的是，在缺乏其他稳定因子的情况下，mrna上的快速翻译起始与不太稳定的eIF4F相互作用相关。本文的在线版本（doi:10.1186/s13059-017-1338-4）包含补充材料，可供授权用户使用。
Translation factors eIF4E and eIF4G form eIF4F, which interacts with the messenger RNA (mRNA) 5′ cap to promote ribosome recruitment and translation initiation. Variations in the association of eIF4F with individual mRNAs likely contribute to differences in translation initiation frequencies between mRNAs. As translation initiation is globally reprogrammed by environmental stresses, we were interested in determining whether eIF4F interactions with individual mRNAs are reprogrammed and how this may contribute to global environmental stress responses. Using a tagged-factor protein capture and RNA-sequencing (RNA-seq) approach, we have assessed how mRNA associations with eIF4E, eIF4G1 and eIF4G2 change globally in response to three defined stresses that each cause a rapid attenuation of protein synthesis: oxidative stress induced by hydrogen peroxide and nutrient stresses caused by amino acid or glucose withdrawal. We find that acute stress leads to dynamic and unexpected changes in eIF4F–mRNA interactions that are shared among each factor and across the stresses imposed. eIF4F–mRNA interactions stabilised by stress are predominantly associated with translational repression, while more actively initiating mRNAs become relatively depleted for eIF4F. Simultaneously, other mRNAs are insulated from these stress-induced changes in eIF4F association. Dynamic eIF4F–mRNA interaction changes are part of a coordinated early translational control response shared across environmental stresses. Our data are compatible with a model where multiple mRNA closed-loop complexes form with differing stability. Hence, unexpectedly, in the absence of other stabilising factors, rapid translation initiation on mRNAs correlates with less stable eIF4F interactions. The online version of this article (doi:10.1186/s13059-017-1338-4) contains supplementary material, which is available to authorized users.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
7.8
作者：
Buchan, J. Ross;Muhlrad, Denise;Parker, Roy
通讯作者：
Parker, Roy
影响因子：
3.3
作者：
Garre, Elena;Romero-Santacreu, Lorena;Alepuz, Paula
通讯作者：
Alepuz, Paula
压力依赖性的固定在动力学和空间上与p-bodies不同的细胞质颗粒的重新定位。
影响因子：
7.8
作者：
Hoyle, Nathaniel P.;Castelli, Lydia M.;Campbell, Susan G.;Holmes, Leah E. A.;Ashe, Mark P.
通讯作者：
Ashe, Mark P.
影响因子：
4.1
作者：
Archer SK;Shirokikh NE;Hallwirth CV;Beilharz TH;Preiss T
通讯作者：
Preiss T